Discussion of “Bayesian forecasting of multivariate time series: scalability,structure uncertainty and decisions”

Annals of the Institute of Statistical Mathematics -     

Supramolecular hydrogel microcapsules via cucurbit[8]uril host–guest interactions with triggered and UV-controlled molecular permeability

Host–guest assembly in droplet-based microfluidics opens a new avenue for fabricating supramolecular hydrogel microcapsules with high monodispersity and controlled functionality. In this paper, we demonstrate a single emulsion microdroplet platform to prepare microcapsules with supramolecular hydrogel skins from host molecule cucurbit[8]uril and guest polymer anthracene-functionalized hydroxyethyl cellulose. In contrast to construction of microcapsules from a droplet-in-droplet double emulsion, here the electrostatic attraction between charged polymer and surfactant facilitates formation of defined supramolecular hydrogel skins in a single emulsion. Furthermore, by taking advantage of dynamic interactions and the tunable cross-linked supramolecular hydrogel network, it is possible to prepare microcapsules with triggered and UV-controlled molecular permeability. These could be potentially used in a delivery system for e.g. agrochemicals, nutraceuticals or cosmetics.     

Layered Black Phosphorus: Strongly Anisotropic Magnetic,Electronic, and Electron‐Transfer Properties

Layered elemental materials, such as black phosphorus, exhibit unique properties originating from their highly anisotropic layered structure. The results presented herein demonstrate an anomalous anisotropy for the electrical, magnetic, and electrochemical properties of black phosphorus. It is shown that heterogeneous electron transfer from black phosphorus to outer‐ and inner‐sphere molecular probes is highly anisotropic. The electron‐transfer rates differ at the basal and edge planes. These unusual properties were interpreted by means of calculations, manifesting the metallic character of the edge planes as compared to the semiconducting properties of the basal plane. This indicates that black phosphorus belongs to a group of materials known as topological insulators. Consequently, these effects render the magnetic properties highly anisotropic, as both diamagnetic and paramagnetic behavior can be observed depending on the orientation in the magnetic field.     

Azasugar inhibitors as pharmacological chaperones for Krabbe disease

Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.     

Hierarchically Structured Allotropes of Phosphorus from Data-Driven Exploration

The discovery of materials is increasingly guided by quantum-mechanical crystal-structure prediction, but the structural complexity in bulk and nanoscale materials remains a bottleneck. Here we demonstrate how data-driven approaches can vastly accelerate the search for complex structures, combining a machine-learning (ML) model for the potential-energy surface with efficient, fragment-based searching. We use the characteristic building units observed in Hittorf's and fibrous phosphorus to seed stochastic (“random”) structure searches over hundreds of thousands of runs. Our study identifies a family of hierarchically structured allotropes based on a P8 cage as principal building unit, including one-dimensional (1D) single and double helix structures, nanowires, and two-dimensional (2D) phosphorene allotropes with square-lattice and kagome topologies. These findings yield new insight into the intriguingly diverse structural chemistry of phosphorus, and they provide an example for how ML methods may, in the long run, be expected to accelerate the discovery of hierarchical nanostructures.